The interests of this laboratory continue to focus on the relationship of bile pigment metabolism to the production and destruction of heme, hemoglobin and red blood cells. Studies are concerned with the pathophysiology of the early-labeled fraction of bile pigment which appears soon after the administration of a labeled precursor such as glycine-2-C14 and is derived from sources other than the breakdown of hemoglobin in senescent red blood cells. Emphasis is given to the mechanisms and implications for disease states of bilirubin production both from nonhemoglobin sources in the liver and from processes related to red blood cell production and hemoglobin synthesis. Investigations of the following specific problems are proposed: studies of alterations in hepatic heme metabolism under pathologic conditions; assessment of possible relationships between the regulation of synthesis of nonhemoglobin hemes in the liver and of hemoglobin heme in the erythroid cells; further elucidation of the mechanisms of bile pigment excretion by the liver; investigation of alternate pathways of bilirubin excretion; and study of the mechanisms and physiologic implications of the process of surface fragmentation or remodelling of immature erythroid cells.